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二恶英类致癌风险——激素作用的例证?

Dioxin cancer risk--example of hormesis?

机构信息

Department of Environmental Health, National Public Health Institute, Kuopio, Finland.

出版信息

Dose Response. 2006 May 1;3(3):332-41. doi: 10.2203/dose-response.003.03.004.

Abstract

A recent case-control study implied an inverse correlation between the measured body burden of dioxins (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans, PCDD/F) and the risk of soft tissue sarcoma in normal population exposed to dioxins mainly via food. The surprising result could not be explained by biases or confounding. There is no a priori confounding by occupational chemicals in a random sample from general population, but exposures to other lipid soluble chemicals with similar sources might be expected to associate with that of dioxins. One such group is polychlorinated biphenyls (PCB). Therefore three most relevant dioxin-like PCB compounds PCB 77, PCB 126, and PCB 169 were now analyzed from the same patients. Cases were 110 soft-tissue sarcoma patients undergoing surgery for their disease, and referents were 227 patients operated for appendicitis. Dioxin and PCB concentrations were analyzed from subcutaneous fat samples by high-resolution gas chromatography-mass spectrometry and TCDD equivalent concentrations (WHO-TEq) were calculated by using toxicity equivalency factors of WHO. The highest risk of sarcoma was found in the septile with the lowest body burden of sum WHO-TEq, and the differences of septiles 2 and 6 from septile 1 were statistically significant. If soft sarcoma risk is true at high occupational levels of dioxins, the provocative result suggests that a possibility of a J-shaped dose-response curve should be taken into consideration and studied further. This is also supported by the similar J-shaped dose responses in animal studies.

摘要

最近的一项病例对照研究表明,在主要通过食物接触二恶英(多氯代二苯并对二恶英和多氯代二苯并呋喃,PCDD/F)的正常人群中,体内二恶英负荷与软组织肉瘤风险之间存在负相关。这一令人惊讶的结果不能用偏差或混杂因素来解释。在一般人群中随机抽取的样本中,没有职业化学品的先验混杂,但人们期望其他来源相似的脂溶性化学物质的暴露与二恶英的暴露有关。多氯联苯(PCB)就是这样一类物质。因此,从同一批患者中分析了三种与二恶英最相关的类似二恶英的 PCB 化合物:PCB 77、PCB 126 和 PCB 169。病例为 110 名因疾病接受手术的软组织肉瘤患者,对照为 227 名因阑尾炎接受手术的患者。通过高分辨率气相色谱-质谱法从皮下脂肪样本中分析二恶英和 PCB 浓度,并使用世界卫生组织的毒性等效因子计算 TCDD 等效浓度(WHO-TEq)。在体内 WHO-TEq 总和最低的百分位数中,发现了最高的肉瘤风险,第 2 百分位数和第 6 百分位数与第 1 百分位数之间的差异具有统计学意义。如果软组织肉瘤的风险确实存在于高水平的职业性二恶英中,那么这一挑衅性的结果表明,应该考虑进一步研究 J 形剂量反应曲线的可能性。动物研究中也存在类似的 J 形剂量反应,这也支持了这一观点。

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